ethyl (S)-<<2-<<(1,1-dimethylethoxy)carbonyl>amino>-3-phenylpropyl>thio>acetate | 134557-84-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl (S)-<<2-<<(1,1-dimethylethoxy)carbonyl>amino>-3-phenylpropyl>thio>acetate
• 英文别名: (S)-[[2-[[(1,1-Dimethylethoxy)carbonyl]amino]-3-phenylpropyl]thio]acetic acid ethyl ester；ethyl 2-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropyl]sulfanylacetate
• CAS: 134557-84-9
• 化学式: C₁₈H₂₇NO₄S
• 分子量: 353.483
• InChiKey: WWRYFIKZVMLFIG-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl (S)-<<2-<<(1,1-dimethylethoxy)carbonyl>amino>-3-phenylpropyl>thio>acetate 在 sodium periodate 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 2.5h， 生成 ethyl (S)-<(2-amino-3-phenylpropyl)sulfinyl>acetate trifluoroacetate
  参考文献：
  名称：

  Rationally designed ‘dipeptoid’ analogues of cholecystokinin (CCK): C-terminal structure-activity relationships of α-methyl tryptophan derivatives

  摘要：

  This paper outlines the synthesis and C-terminal structure-activity relationships (SAR) of a series of alpha-methyl tryptophanylphenethylamide analogues of the neuropeptide cholecystokinin (CCK). CCK-B and CCK-A receptor binding affinities of these analogues are described and the contributions of the various side chains on the phenethylamide moiety to binding affinity are discussed. Several of the compounds prepared have CCK-B receptor binding affinities similar to that found with the endogenous neuropeptide CCK-26-33 (sulphated) (CCK-B, IC50 = 0.3 nM) and are highly selective over the CCK-A receptor. Amongst the most potent of the compounds synthesized are [R-(R*,S*)]-beta-4[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)carbonyl]-amino]propyl]amino]benzenebutanoic acid 22, [R-(R*,S*)]-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)carbonyl]amino]propyl]amino]-3-phenylpropyl] thio]acetic acid 28a and [R-(R*,S*)]-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)carbonyl]amino]propyl]amino]-3-phenylpropyl]sulfonyl]acetic acid 32 which have CCK-B receptor binding affinities of IC50 = 0.3, 0.3 and 0.2 nM with CCK-A/B ratios of 220, 700 and 1000, respectively. CCK-B receptor selective ligands, 22, 28a and 32 were also shown to be potent antagonists in blocking pentagastrin-evoked excitation in neurons of the rat hypothalamic ventro-medial nucleus (VMN) with the K(e) values of 2.8, 23 and 5.9 nM, respectively.

  DOI：

  10.1016/0223-5234(93)90078-s
• 作为产物：
  描述：

  N-Boc-L-苯丙氨醇 在 吡啶 、 sodium hydride 作用下， 反应 72.67h， 生成 ethyl (S)-<<2-<<(1,1-dimethylethoxy)carbonyl>amino>-3-phenylpropyl>thio>acetate
  参考文献：
  名称：

  Rationally designed ‘dipeptoid’ analogues of cholecystokinin (CCK): C-terminal structure-activity relationships of α-methyl tryptophan derivatives

  摘要：

  This paper outlines the synthesis and C-terminal structure-activity relationships (SAR) of a series of alpha-methyl tryptophanylphenethylamide analogues of the neuropeptide cholecystokinin (CCK). CCK-B and CCK-A receptor binding affinities of these analogues are described and the contributions of the various side chains on the phenethylamide moiety to binding affinity are discussed. Several of the compounds prepared have CCK-B receptor binding affinities similar to that found with the endogenous neuropeptide CCK-26-33 (sulphated) (CCK-B, IC50 = 0.3 nM) and are highly selective over the CCK-A receptor. Amongst the most potent of the compounds synthesized are [R-(R*,S*)]-beta-4[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)carbonyl]-amino]propyl]amino]benzenebutanoic acid 22, [R-(R*,S*)]-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)carbonyl]amino]propyl]amino]-3-phenylpropyl] thio]acetic acid 28a and [R-(R*,S*)]-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)carbonyl]amino]propyl]amino]-3-phenylpropyl]sulfonyl]acetic acid 32 which have CCK-B receptor binding affinities of IC50 = 0.3, 0.3 and 0.2 nM with CCK-A/B ratios of 220, 700 and 1000, respectively. CCK-B receptor selective ligands, 22, 28a and 32 were also shown to be potent antagonists in blocking pentagastrin-evoked excitation in neurons of the rat hypothalamic ventro-medial nucleus (VMN) with the K(e) values of 2.8, 23 and 5.9 nM, respectively.

  DOI：

  10.1016/0223-5234(93)90078-s

文献信息

• N-substituted cycloalkyl and polycycloalkyl .alpha.-substituted Trp-Phe-
  申请人：Warner-Lambert Company

  公开号：US05631281A1

  公开（公告）日：1997-05-20

  Novel unnatural dipeptoids of .alpha.-substituted Trp-Phe derivatives useful as agents in the treatment of obesity, hypersecretion of gastric acid in the gut, gastrin-dependent tumors, colorectal tumors, or as antipsychotics are disclosed. Further the compounds are antianxiety agents, antiulcer agents, antidepressant agents, and are agents useful for preventing the withdrawal response produced by chronic treatment or use followed by chronic treatment followed by withdrawal from nicotine, diazepam, alcohol, cocaine, caffeine, or opiods. Also disclosed are pharmaceutical compositions and methods of treatment using the dipeptoids as well as processes for preparing them and novel intermediates useful in their preparation. An additional feature of the invention is the use of the subject compounds to prepare pharmaceutical and diagnostic compositions.

  揭示了作为治疗肥胖、肠道胃酸过多、胃泌素依赖性肿瘤、结肠肿瘤或抗精神病药物的α-取代Trp-Phe衍生物的新型非天然二肽类化合物。此外，这些化合物还是抗焦虑剂、抗溃疡剂、抗抑郁剂，并且可用作预防慢性治疗或使用后的戒断反应，包括尼古丁、安定、酒精、可卡因、咖啡因或阿片类药物的慢性治疗后随后的戒断反应。还公开了使用这些二肽类化合物的药物组合物和治疗方法，以及用于制备它们的过程和在其制备中有用的新型中间体。该发明的另一个特点是使用这些化合物来制备药物和诊断组合物。
• N-substituted cycloalkyl and polycycloalkyl alpha-substituted Trp-Phe- and phenethylamine derivatives
  申请人：Warner-Lambert Company LLC

  公开号：EP0405537B1

  公开（公告）日：2004-09-08
• N-SUBSTITUTED CYCLOALKYL AND POLYCYCLOALKYL ALPHA-SUBSTITUTED Trp-Phe- AND PHENETHYLAMINE DERIVATIVES
  申请人：Warner-Lambert Company

  公开号：EP0479910A1

  公开（公告）日：1992-04-15
• US5278316A
  申请人：——

  公开号：US5278316A

  公开（公告）日：1994-01-11
• US5580896A
  申请人：——

  公开号：US5580896A

  公开（公告）日：1996-12-03